Minerva Carrasquillo
Evaluating the role of pathogenic dementia variants in posterior cortical atrophy
Carrasquillo, Minerva; Barber, Imelda S.; Lincoln, Sarah J.; Murray, Melissa E.; Camsari, Gamze Balci; Khan, Qurat ul Ain; Nguyen, Thuy; Ma, Li; Bisceglio, Gina D.; Crook, Julia E.; Younkin, Steven G.; Dickson, Dennis W.; Boeve, Bradley F.; Graff-Radford, Neill R.; Morgan, Kevin; Ertekin-Taner, Nil�fer
Authors
Imelda S. Barber
Sarah J. Lincoln
Melissa E. Murray
Gamze Balci Camsari
Qurat ul Ain Khan
Thuy Nguyen
Li Ma
Gina D. Bisceglio
Julia E. Crook
Steven G. Younkin
Dennis W. Dickson
Bradley F. Boeve
Neill R. Graff-Radford
Kevin Morgan
Nil�fer Ertekin-Taner
Abstract
Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX.
Citation
Carrasquillo, M., Barber, I. S., Lincoln, S. J., Murray, M. E., Camsari, G. B., Khan, Q. U. A., Nguyen, T., Ma, L., Bisceglio, G. D., Crook, J. E., Younkin, S. G., Dickson, D. W., Boeve, B. F., Graff-Radford, N. R., Morgan, K., & Ertekin-Taner, N. (2016). Evaluating the role of pathogenic dementia variants in posterior cortical atrophy. Neurobiology of Aging, 37, https://doi.org/10.1016/j.neurobiolaging.2015.09.023
Journal Article Type | Article |
---|---|
Publication Date | Jan 1, 2016 |
Deposit Date | Mar 14, 2016 |
Publicly Available Date | Mar 14, 2016 |
Journal | Neurobiology of Aging |
Print ISSN | 0197-4580 |
Electronic ISSN | 1558-1497 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 37 |
DOI | https://doi.org/10.1016/j.neurobiolaging.2015.09.023 |
Keywords | PCA, poserior Alzheimer's disease, dementia, APOE, TREM2, PSEN2, NeuroX |
Public URL | https://nottingham-repository.worktribe.com/output/978808 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0197458015004807 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
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